NIH Phase II-UNCD as Bio-Inert Interface for Anti-Thrombogenicity Applications in

描述(申请人提供)：包括心脏辅助装置(VAD)和机械心脏瓣膜(MHV)在内的人工心血管装置(ACD)已经植入数百万患者体内，以挽救或改善他们的生活。ACD植入物的日益成功伴随着一个不幸的事实，即这些患者必须服用强大的抗凝药物，并保持血液中的临界剂量水平，以避免血栓形成或出血。考虑到个别患者的并发症和世界范围内巨大的病例负荷，长期的抗凝剂维护在个人、社会和经济上都是昂贵的。此外，大多数怀孕和免疫受损的患者通常不能服用抗凝剂。先进钻石技术公司(ADT)建议通过为ACDs的所有免疫触发表面引入一种生物兼容的界面材料--超纳米晶体钻石(UNCD(R))来消除血栓，而不需要抗凝剂的帮助。UNCD是一种由申请人开发的极其光滑、坚硬和低成本的多晶钻石。在第一阶段项目中，作为世界上的第一个项目，UNCD被成功地集成在Jarvik 2000(R)心脏VAD上，并植入绵羊体内，绵羊存活了3周，没有受到钻石涂层的不利影响。在绵羊体内植入的VAD中最小的血栓积聚表明UNCD将是一种近乎理想的抗血栓材料。借助合作伙伴的合作和从第一阶段工作中获得的经验，通过这一第二阶段项目，UNCD涂层的ACDs将发展到接近商业阶段。基于复杂的UNCD涂层技术，目标将从短期VAD植入物扩展到长期ACD，主要是机械心脏瓣膜(MHV)，并与Jarvik心脏和Meril生命科学公司密切合作。第二阶段的目标将解决第一阶段中确定的令人担忧的问题，例如，将粘附性提高到针对长期植入的极其强大的水平。在MHV的主要材料--热解碳(PYC)方面，涂层的一个主要挑战也将被解决。作为将我们的技术转化为产品的关键一步，ADT将与俄克拉荷马州立大学合作，研究UNCD涂层的ACDs的生物兼容性、血流动力学和耐用性。如果该项目成功，UNCD VAD和MHV的潜在美国市场每年分别至少为40,000和250,000台，全球UNCD涂层的总价值超过4亿美元。更重要的是，这种新型抗血栓材料的成功应用对人类、社会和经济的影响将是惊人的。正如MHV的创始人之一戈特博士在他的综述中所评论的那样，“最终，有了正确的瓣膜设计和正确的瓣膜材料，我们有一天可能会拥有一种不需要终身抗凝治疗的机械瓣膜。”我们正在努力，期望联合国儿童基金会成为这一“合适的材料”。

DESCRIPTION (provided by applicant): Artificial cardiovascular devices (ACDs) including ventricular assist devices (VADs) and mechanical heart valves (MHVs) have been implanted into millions of patients, to save or improve their lives. The increasing success of ACD implants has been accompanied with the unfortunate fact that these patients have to take powerful anticoagulant drugs and maintain a critical dosage level in the blood to avoid thrombosis or hemorrhage. Long-term anticoagulant maintenance is individually, socially and economically expensive considering the complications to individual patients and the huge world-wide case load. In addition, most pregnant and immune compromised patients cannot normally take anticoagulants. Advanced Diamond Technologies (ADT) proposes to eliminate thrombus without the help of anticoagulants, by introducing a biocompatible interface material, Ultrananocrystalline diamond (UNCD(r)), for all the immune-triggering surfaces of ACDs. UNCD is an extremely smooth, hard, and low-cost polycrystalline diamond developed by the applicant. In the Phase I project, as a world first, UNCD was successfully integrated on a Jarvik 2000(r) heart VAD and implanted into a sheep which survived for 3 weeks with no adverse consequences from the diamond coating. The minimal thrombus build-up in the VAD implanted in the sheep suggests UNCD will be a near-ideal anti-thrombogenic material. With the partner collaboration and experience gained from the Phase I work, UNCD coated ACDs will be developed to near commercial stage through this Phase II project. Based on the sophisticated UNCD coating technology, the goal will be expanded from short term VAD implants to the long term ACD, mainly mechanical heart valve (MHV) in close collaboration with Jarvik Heart and Meril Life Science. The Phase II goals will address the issues of concern identified in Phase I, e.g., improving adhesion to an extremely robust level targeting long-term implantation. A major coating challenge in terms of the principle material for MHVs, pyrolytic carbon (PyC), will be addressed too. As a key step to bridge our technique to a product, ADT will work with Oklahoma State University to study the biocompatibility, hemodynamics and durability of the UNCD coated ACDs. If the project is successful, the potential US market for UNCD VADs and MHVs is at least 40,000 and 250,000 units respectively per year, over $400 million in total for UNCD coating worldwide. More importantly, the human, societal, and economic implications of the successful application of this novel antithrombogenic material would be staggering. As Dr. Gott, one of the fathers of the MHV commented in his review, "Eventually, with the right valve design and the right valve material, it is conceivable that we may someday have a mechanical valve that does not require lifelong anticoagulation therapy." We are making effort with an expectation that UNCD will be this "right material."